This proposal explores further the biology of human tumors which secrete significant quantities of small peptide hormones. We seek to establish how patterns of protein content in tumors such as medullary thyroid carcinoma and small cell lung carcinoma reflect their lines of differentiation, cellular makeup, and evolvement with time and metastatic spread. The relationship of peptide hormone synthesis to stages of neuroendocrine maturation will be explored. The specific projects involved include: 1) Efforts to understand the high activity of the amine metabolizing enzyme histaminase (diamine oxidase) in some tumors. Newly developed affinity procedures are used to purify human histaminase from normal and malignant tissues; the isolated enzymes are subjected to comparative biochemical and immunological analyses. Immunohistochemical techniques are used to detail the cellular location of histaminase. The biologic function of the enzyme and its relationship to polyamine metabolism is under study in regenerating epithelial cells. 2) The dual synthesis of biogenic amines and peptide hormones by tumors is under study. We seek to define the role of the amines for synthesis and secretion of hormones and whether these two synthetic pathways reflect the presence of the same or different lines of cellular differentiation in peripheral endocrine tissues and tumors. A profile of biochemistry has been established for this purpose including biochemical assays and/or immunohistochemical localization of calcitonin, vasoactive intestinal peptide, ACTH, L-dopa decarboxylase and histaminase. The relationship of this profile to stages of differentiation of familial medullary thyroid carcinoma, bronchial epithelium, lung tumors, "APUD" vs. "non-APUD" tumors and an in vitro model of neural maturation (neuroblastoma-ganglioneuroma cells in culture) is investigated. The clonal vs. multiclonal origin of tumors with "APUD" properties is being matched with the profiles of biochemistry studied.